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Blood samples for big endothelin and NT-proBNP were taken every two hours during a standartised daily regime.
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ORM-10962 significantly reduced the inward/outward NCX currents with estimated EC50 values of 55/67 nM, respectively. The compound, even at a high concentration of 1 μM, did not modify significantly the magnitude of ICaL in CMs, neither had any apparent influence on the inward rectifier, transient outward, the rapid and slow components of the delayed rectifier potassium currents, the late and peak sodium and Na+/K+ pump currents. NCX inhibition exerted moderate positive inotropic effect under normal condition, negative inotropy when reverse, and further positive inotropic effect when forward mode was facilitated. In dog Purkinje fibres 1 μM ORM-10962 decreased the amplitude of digoxin induced delayed afterdepolarizations (DADs). Pre-treatment with 0.3 mg/kg ORM-10962 (i.v.) 10 min before starting ouabain infusion significantly delayed the development and recurrence of ventricular extrasystoles (by about 50%) or ventricular tachycardia (by about 30%) in anesthetized guinea pigs. On the contrary, ORM-10962 pre-treatment had no apparent influence on the time of onset or the severity of I/R induced arrhythmias in anesthetized rats and in Langendorff perfused guinea-pig hearts.
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This study was carried out in a tertiary referral centre.
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654 patients over 15, men and women, who attended the emergency service between October and December 1997. 354 of them had an ARM (cases) and 300 did not (controls).
No single therapy is associated with a uniformly improved outcome for the involved twins and success is primarily related to gestational age and severity at diagnosis. Standard therapy has commonly been serial amnioreduction, which appears to improve the overall outcome. Intertwin sepstostomy similary improves outcome but has no survival advantage over serial amnioreduction. Selective fetoscopic laser photocoagualtion has emerged as an alternative treatment strategy in TTTS with at least comparable if not superior survival to serial amnioreduction. TTTS diagnosed before 26 weeks' gestation has significantly better survival rates and fewer neurological sequelae after laser therapy than amnioreduction.
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Effects of verapamil and diltiazem on hemodynamics, ventricular response in AF, clinical parameters and mortality were reviewed.
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In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors.
Acecainide (N-acetylprocainamide), the N-acetylated metabolite of procainamide, is a Class III antiarrhythmic agent. It can be given either intravenously or orally, and is eliminated primarily by renal excretion. In a small number of noncomparative and placebo-controlled short term therapeutic trials acecainide markedly reduced premature ventricular beats and prevented induction of ventricular tachycardia in more than 70% of patients following intravenous administration and in about 50% after oral administration. Acecainide was effective in about one-quarter of patients refractory to other antiarrhythmic drugs. Interpretation of its effectiveness following long term oral therapy is complicated by the limited number of patients, and patients discontinuing due to adverse effects or lack of efficacy. However, about 40% of the small number treated for extended periods were controlled for periods of 6 months to 3 to 4 years. Comparative studies with other antiarrhythmic drugs have not been undertaken apart from a small study in atrial flutter where acecainide was better than quinidine plus digoxin. Thus, although further clinical experience is required before the relative place of acecainide in therapy can be determined, the drug nevertheless appears to offer advantages over procainamide, particularly with respect to the reduced formation of antinuclear antibodies.
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The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg.
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The effect of a therapeutic dose of oral salbutamol on serum and skeletal muscle digoxin concentrations has been studied in volunteers digitalised with digoxin. On one occasion a biopsy was taken from the quadriceps after 2 h of supine rest and then 3-4 mg salbutamol was given orally. Blood samples were taken before and after that dose and another muscle biopsy specimen was taken from the same thigh 180 min after the medication. On another occasion control blood sampling, ECG and blood pressure recordings were made but without muscle biopsies or salbutamol administration. Compared to the control measurements, salbutamol decreased the serum digoxin concentration (0.30 nmol.l-1). It also reduced the serum potassium concentration (0.58 mmol.l-1). The digoxin concentration in skeletal muscle did not change significantly after the intake of salbutamol. Thus, even a therapeutic oral dose of salbutamol reduces the serum digoxin concentration in man.
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Non-compliance has a major influence on the successful outcome of a therapeutic regimen. It also unnecessarily increases the costs of health care. In a study involving 137 outpatients receiving digoxin 55 patients (40%) were found to be non-compliant. Patients who experienced communication problems and who lacked a meaningful relationship with their doctor showed a marked deterioration in compliance. An applied pharmacokinetic approach was used to predict the serum digoxin concentration for each patient. The creatinine clearance was determined and the degree of severity of heart failure was assessed. Total body clearance was then calculated. The predicted concentration was also calculated and compared with the measured digoxin concentration enabling an objective assessment of compliance. Twenty-four of the non-compliant patients who had subtherapeutic levels of digoxin (less than 0.8 ng/ml) had signs of cardiac failure. Eighteen of these patients were receiving additional medication (1.7 +/- 0.5 items) for the treatment of cardiac failure.
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Despite its seldom occurrence, fetal tachycardia can lead to poor fetal outcomes including hydrops and fetal death. Management can be challenging and result in maternal adverse effects secondary to high serum drug levels required to achieve effective transplacental antiarrhythmic drug therapy.
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Emergencies in pediatric cardiology are heart failure, cyanosis and rhythm disturbances. The signs of heart failure are tachycardia, tachypnea and hepatomegaly. The therapy consists of oxygen, diuretics and digoxin. Occasionally, intubation with mechanical ventilation and intravenous catecholamines are needed. Cyanosis is often the only sign of a severe heart malformation, and prompt hospitalization is mandatory. Oxygen and warm environment is important during transport, correction of a possible metabolic acidosis and prostaglandin infusion are done in the hospital. Beyond the newborn period, so-called cyanotic spells are seen, particularly in tetralogy of Fallot. In supraventricular tachycardia, vagal manoeuvres can be tried first, if not successful, intravenous adenosine or electroconversion will restore sinus rhythm. In the older child, intravenous isoptin can be given. Slow heart rates from total AV block or sinus node affection are treated with atrophic, isuprel or electrical pacing.
Alerts were implemented to notify of the potential risk from low electrolyte concentrations or unknown digoxin or electrolyte concentrations during CPOE. Alerts were also generated in response to newly reported hypokalemia and hypomagnesemia in patients given digoxin.
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Therapeutic "digoxin level" monitoring in selected wards was audited. Time elapsing between the last dose and blood sampling was considered appropriate if greater than or equal to 6 h. If such details were not entered on the requisition, the maximum time elapsing was estimated as "appropriate" or "inappropriate" from the time samples were logged into the laboratory and the time the last dose was entered in the patient's treatment sheet. In 22 requisitions detailing sampling time, nine were considered inappropriate. In an additional 150 instances, timing was estimated as inappropriate in 45. Among the 118 requests where timing (estimated or labelled) was appropriate, available plasma digoxin concentrations yielded a mean of 1.0 nM, compared to 1.6 nM in the corresponding 54 patients with premature sampling; this difference was both clinically and statistically significant (95% confidence limits 0.8-1.2 and 1.3-1.9 nM, respectively, p less than 0.001). Premature blood sampling for digoxin levels was common and associated with higher concentrations than when appropriate. Such inappropriate timing may not have serious consequences, but digoxin levels are a matter of record and are used for teaching; due attention to timing could provide more reliable information and avoid wasting valuable resources.
After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations.
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104 patients were analysed. The percentage of HF was 13.76%. 52.88% were men with an average age of 72.16 +/- 17.78 year. Average age for women was 82.92 +/- 7.24 year. The main cause of admission was dysnea (74%). Hypertension was the principal risk factor (70.13%). When it comes to aetiology, HTA (68.57%) was the main one. Global and left HF (33.65% either) were the most common type of HF. 5.17% of women and 20.69% of men suffered from systolic dysfunction (p < 0.023). 32.76% of women and 41.38% of men had diastolic dysfunction. The base treatment-on-release for the majority of patients consisted of diuretics and digoxin. Patients stayed 15.49 days on average, and the number of readmitted ones came up to 26.67%.
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Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions for the 3D regimen of OBV, PTV/r, and DSV and various medications in healthy volunteers to inform dosing recommendations in HCV-infected patients.
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Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator.
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The objective of this study was to assess the effect of a physician-focused, multi-factorial, quality-improvement intervention on PIM prescribing in older patients in primary care.
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Several transporter systems in the liver and intestine are known to change their expression and function during cholestatic disease states. The objective of the present in vivo study was to investigate the effect of biliary depletion, as a method to mimic cholestasis, on the bioavailability and disposition of digoxin in biliary and pancreatic duct cannulated pigs. The study was divided in two parts. In the first part, a solution of 10 microg/kg digoxin was administered intravenously to the cannulated pigs with intact enterohepatic circulation (Control) and during depletion of the bile and pancreatic juice. In the second part, the same dose of digoxin was administered intraduodenally with intact enterohepatic circulation (Control) and during depletion of either bile or pancreatic juice or both. Biliary depletion decreased the flow of bile and pancreas juice as well as the amount of digoxin appearing in the bile. Deprivation of both bile and pancreas juice significantly increased the bioavailability of digoxin, the plasma AUC after enteral administration increased from 17.6+/-4.2 nmol/lh (Control) to 29.6+/-8.3 nmol/lh (P<0.05). The biliary clearance decreased significantly, from 0.22+/-0.11 l/h/kg (Control) to 0.04+/-0.03 l/h/kg during pancreatic and biliary depletion (P<0.05). There was a significant decrease in elimination half-life (P<0.05) and volume of distribution (P<0.01) during the depletion experiments while the systemic clearance remained unchanged. The results clearly suggest that biliary depletion trigger a short-term downregulation, most likely posttranscriptionally mediated, of a sinusoidal uptake transporter in the liver, possibly a pig ortholog of OATP.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists; amiodarone; angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; anticoagulation; antiplatelet agents; beta-blockers; calcium channel blockers; cardiac resynchronisation therapy; digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors); exercise; hydralazine plus isosorbide dinitrate; implantable cardiac defibrillators; multidisciplinary interventions; non-amiodarone antiarrhythmic drugs; and positive inotropes (other than digoxin).
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To evaluate the appropriateness and utility of SDCs ordered in a medical group practice setting by categorizing the reason the SDC was ordered and identifying action taken in response to the result.
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Using mathematical analysis and computer simulation, we studied the effect of gamma scintillation counting error on two radioimmunoassays (RIAs) and an immunoradiometric assay (IRMA). To analyze the propagation of the counting errors into the estimation of analyte concentration, we empirically derived parameters for logit-log data-reduction models for assays of digoxin and triiodothyronine (RIAs) and ferritin (IRMA). The component of the analytical error attributable to counting variability, when expressed as a CV of the analyte concentration, decreased approximately linearly with the inverse of the square root of the maximum counts bound. Larger counting-error CVs were found at lower concentrations for both RIAs and the IRMA. Substantially smaller CVs for overall assay were found when the maximum counts bound progressively increased from 500 to 10,000 counts, but further increases in maximum bound counts resulted in little decrease in overall assay CV except when very low concentrations of analyte were being measured. Therefore, RIA and IRMA systems based in duplicate determinations having at least 10,000 maximum counts bound should have adequate precision, except possibly at very low concentrations.
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Ejection fraction improvement is an independent predictor of long-term outcome in revascularized patients but viability (low-dose wall motion score) and digoxin use in follow-up are also independent predictors and add incremental prognostic value to ejection fraction improvement.
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We performed secondary analysis of data from a postmarketing surveillance study of patients with life-threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function.
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OBJECTIVE.: Infants with single ventricle physiology have a high mortality and poor somatic growth during the interstage period. We retrospectively assessed the impact of pharmacotherapy in this population using a multicenter database. DESIGN AND RESULTS.: Records for 395 patients (63.5% boys) with single ventricle were obtained from the National Pediatric Cardiology Quality Improvement Collaborative registry. Median of five medications were prescribed per patient at discharge after stage 1 palliation (interquartile range 3 to 6); the most common medications being aspirin (95.7%), diuretics (90.4%), angiotensin convertase enzyme inhibitors (37.7%), proton pump inhibitors (33.4%), H2 receptor blockers (30.6%), and digoxin (27.6%). Interstage mortality was 9.4%. Digoxin use was associated with lower risk of death (P =.03) on univariable analysis, however no single medication was an independent predictor on regression analysis. Change in weight-for-age z-score was studied as outcome of somatic growth with 36.3% patients showing a decrease during the interstage period. Total number of medications prescribed to a patient showed a negative correlation with the interstage change in z-score (r = -0.19, P =.002). On univariable comparisons, use of metoclopramide and lansoprazole were associated with decreased z-score (P =.004 and.041, respectively) although linear regression failed to identify any agent as independent predictor. CONCLUSIONS.: Children with single ventricle have high mortality and a profound medication burden. No individual medication is independently associated with better survival or weight gain during interstage period. Despite widespread use, proton pump inhibitors and prokinetic agents are not associated with better outcomes and may be associated with poor growth.
1.4% of hospitalized patients in medical wards experienced potentially preventable ADE. Healthcare professionals and administrators must be made aware of the scope of this problem so that they will implement effective safety practices directed to reduce the incidence of medication errors, particularly prescription and monitoring errors.